What is retinopathy of prematurity?

Retinopathy of prematurity is a disease of the retinal blood vessels that can occur in extremely premature infants. The retina is the inner lining of the eye that consists of specialized nerve cells necessary for sight. Blood vessels in the retina develop first from the optic nerve area at the very back of the eye, with growth of blood vessels within the retina toward the front of the eye. The normal process of retinal blood vessel growth is stopped in premature infants, leading to the formation of abnormal blood vessels and scar tissue.

What causes retinopathy of prematurity?

Researchers have discovered several risk factors for retinopathy of prematurity. One of the most significant risk factors is prematurity (born before 34 weeks of pregnancy). Another risk factor is low birth weight (less than 1500 grams or approximately 3 pounds). In the past, extremely high levels of oxygen therapy necessary for the survival of premature infants were thought to contribute to retinopathy of prematurity. However, with the precision of modern oxygen monitoring techniques now available, it is unlikely that excess oxygen causes this disease. Retinopathy of prematurity also has been reported in infants who receive no supplemental oxygen. In experiments, retinopathy of prematurity has been produced in animals by conditions simulating low-oxygen levels.

Who gets retinopathy of prematurity?

Infants weighing less than 1250 grams have an approximately 50% chance of developing some retinopathy of prematurity. As birth weight decreases, the likelihood of retinopathy of prematurity increases. More than 90% of infants weighing less than 750 grams develop retinopathy of prematurity. The same trend holds true in relation to when an infant is born. Approximately 30% of infants after 32 weeks of pregnancy develop retinopathy of prematurity, and greater than 80% of infants less than 28 weeks of pregnancy develop retinopathy of prematurity.

How does it cause disease?

The growth of normal retinal blood vessels may be stopped, with normal vessels only growing to the middle of the retina. Beyond this, the retina has no blood vessels. Most likely, a chemical signal is then sent out that stimulates the remaining retina to grow new blood vessels. The new blood vessels are abnormal and frail, and they can bleed and scar easily. If enough of this scar tissue is present, it can pull on the retinal tissue, causing a traction retinal detachment. If the situation progresses further, a total retinal detachment can occur, leading to vision loss and, possibly, loss of the eye.

Common findings

An ophthalmologist experienced in the examination for this condition can diagnose retinopathy of prematurity. A set of dilating drops is placed in each eye to dilate the pupil. The infant is examined with an instrument to keep the eyelids open (called a lid speculum), and the retina is inspected with an ophthalmoscope. The eyeball may be manipulated to complete the examination.

The area (zone) of retinal involvement and the severity (stage) of the disease define retinopathy of prematurity.

Zone I is a circular area, roughly equivalent to the optic nerve and macular area in the center of the retina. Zone II is a larger circle surrounding this area, roughly equivalent to the middle of the retina. Zone III is the remaining anterior (or front) retina and represents an area of near maturity of the retinal vessels. Severe retinopathy of premature occurs most often in Zones I and II.

Stage I is defined as a line found at the border of the normal retina and the retina without blood vessels. Stage II is defined as a thickening of the line to form what is called a ridge. These stages probably represent growth of immature retinal cells. Stage III involves growth of new abnormal blood vessels, both on the ridge and elevated above the ridge into the vitreous (clear, gelatinous material between the retina and the lens) area. When Stage III blood vessel growth reaches a certain level, it is best treated by laser. Stage IV involves traction and detachment of the retina. This stage is divided into Stage IV-A, or detachment not involving the macula (area near the center of the retina where vision is most clear), and Stage IV-B, or detachment involving the macular or central retina. Stage V is defined as a total tractional retinal detachment for which there is often no effective treatment.

Plus disease is defined by abnormal vessels that are very tortuous, along with the findings listed above, usually indicating a situation that may require immediate treatment. Rush disease indicates unusually fast progression (1- to 2-week period) from no retinopathy of prematurity to disease that requires treatment.

Most retinopathy of prematurity does not require treatment and resolves on its own. The risk of developing disease that requires treatment is highly related to low birth weight and prematurity. In infants weighing less than 750 grams (approximately 1 1/2 pounds), 15% to 20% of infants developing any retinopathy of prematurity do go on to disease that requires treatment. For infants weighing greater than 1250 grams (approximately 2 3/4 pounds), only 2% of infants developing retinopathy of prematurity go on to disease needing treatment. Some retinopathy of prematurity that develops in the remainder of the infants ultimately resolves on its own.

Treatment

Earlier studies found a beneficial effect of cryotherapy (freezing treatment) to the peripheral areas of the retina (areas without blood vessels) in healing retinopathy of prematurity. Now, cryotherapy has been replaced largely by laser treatment. In both treatments, the peripheral areas of the retina are destroyed, leading to a decreased demand for the growth of new blood vessels. The abnormal new blood vessels then are seen to shrink away, leaving no further effect on the retina.

The ophthalmologist delivers the laser treatment through the dilated pupil with an indirect ophthalmoscope system (similar to the setup used for examination). The treatment generally takes 30-45 minutes per eye, and it often is performed in the neonatal intensive care setting. Intravenous (IV) sedation and pain relief commonly are used, and a breathing tube sometimes is necessary.

The infant usually is reexamined at 2-4 weeks. Re-treatments of problem areas occasionally are necessary. Progression of severe retinopathy of prematurity can occur despite successful cryotherapy or laser treatment. A small percentage of eyes continue on to traction retinal detachment despite adequate treatment.

What are the complications?

Continued retinopathy of prematurity with traction retinal detachment and loss of vision is the final outcome in some cases, although this risk is reduced greatly with well-timed treatment. Even if retinopathy of prematurity resolves on its own or if treatment is required, certain outcomes are common, including nearsightedness (difficulty seeing things far away). Other possible complications include amblyopia (weakened vision in one eye) or strabismus (misalignment of the eyes) with an eye deviating in (esotropia) or out (exotropia) when compared to the other eye. A pediatric ophthalmologist can address all these conditions in the follow-up stage.

Complications of laser treatment or cryotherapy include corneal burns or swelling (edema), lens burns or cataract formation, and vitreous hemorrhage or bleeding into the center cavity of the eye. As mentioned above, retinal traction and detachment can occur despite treatment.

How do you prevent it?

No proven treatment exists to prevent the occurrence of retinopathy of prematurity in infants who are at an increased risk. Careful monitoring of oxygenation status and examination of high-risk infants at 6 weeks after birth effectively identifies cases of retinopathy of prematurity that may need additional treatment. No correlation exists between lighting conditions in the nursery and the development of retinopathy of prematurity.

What research is being done?

The effect of supplemental oxygen on infants with Stage III is being studied in the STOP-ROP (Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity) trial. The initial results from this study indicate no firm beneficial effect of increasing oxygenation in Stage III of this condition. The multicenter CRYO-ROP (Cryotherapy for Retinopathy of Prematurity) study continues to observe infants in a phase III long-term follow-up study.

The Committee Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol. 1984 Aug;102(8):1130-1134.

The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. II. The classification of retinal detachment. Arch Ophthalmol. 1987 Jul;105(7):906-912.

David W. Johnson, MD, is an ophthalmologist in private practice specializing in vitreoretinal surgery. He currently holds a teaching appointment as Assistant Clinical Professor in the Department of Ophthalmology at the University of Colorado Health Sciences Center in Denver. Dr. Johnson actively participates in the diagnosis and treatment of retinopathy of prematurity at several Denver area hospitals.